Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the feasibility of performing non-radioactive in situ hybridization (ISH) in flow cytometrically sorted (tumor) cells with a chromosome #1 specific centromere probe. The study was performed in a model system of HL60 cells mixed with different quantities of HeLa cells. These latter cells were sorted directly onto poly-l-lysine coated glass slides on the basis of their keratin content, a cytoskeletal component not present in HL60 cells. Overall morphology of the separated HeLa cells was excellent and, after the ISH procedure, the appropriate number of ISH spots was observed in more than 85% of the sorted cells. This percentage did not differ significantly in cell mixtures with different percentages of HeLa cells (down to 1%). Sorting of HeLa cells in different phases of the cell cycle, and subsequent ISH, revealed the same spot number for chromosome #1 in all cell cycle stages, including mitosis. In the latter phase of the cell cycle we did not find a duplication of the chromosome #1 centromere, not even after sorting of the mitotic cells on the basis of specific labeling with an antibody to mitotin. The early G2 mitotin negative fraction, however, showed a significant percentage of cells with a duplicate spot number, most likely representing a tetraploid cell fraction in this HeLa cell culture. The protocol that evolved from these model studies was applied to cell suspensions of malignant body cavity effusions as well as solid bladder carcinomas. In several of these cases numerical chromosome aberrations could be detected by ISH more evidently after sorting on the basis of keratin labeling.
 ...
PMID:Chromosome detection by in situ hybridization in cancer cell populations which were flow cytometrically sorted after immunolabeling. 138 8

Degradation products of peptidoglycan, the universal bacterial cell wall constituent, were previously found in animal tissues and urine. Reassessment and quantitative analysis of available data lead to an original concept, i.e. that eukaryotic cells synthesize peptidoglycan. We present a model in which this endogenously synthesized peptidoglycan is essential for the processes of eukaryotic cell division and sleep induction in animals. Genes for peptidoglycan metabolism, like those for lysine biosynthesis in plants, are probably inherited from endosymbiotic bacteria, the ancestors of mitochondria and chloroplasts. Corollaries of this concept, i.e. roles for peptidoglycan metabolism in tumor formation and in the biological clock, are supported by abundant evidence. We propose that many interactions between bacteria and eukaryotes are conditioned by their common genetic heritage.
 ...
PMID:Endogenous synthesis of peptidoglycan in eukaryotic cells; a novel concept involving its essential role in cell division, tumor formation and the biological clock. 142 43

A rapid separation of polyamines and some related amino acids in cultured tumor cells by high-performance capillary zone electrophoresis with indirect photometric detection is demonstrated. 60 cm x 75 microns I.D. fused-silica capillary was used for the separation and quinine sulfate was used as a background electrolyte (BGE). Several polyamines (putrescine, spermidine and spermine), amino acids (lysine, arginine, histidine) and simple cations (K+, Na+) were easily separated in less than 10 min. Using the indirect photometric detection method, femtomole amounts of polyamines extracted from the tumor cells were detected from nanoliter injection volumes, and the signal response was linear over two orders of magnitude.
 ...
PMID:Indirect photometric detection of polyamines in biological samples separated by high-performance capillary electrophoresis. 143 36

Gene and protein expression of Y-79 retinoblastoma cells growing on poly(D-lysine) is switched from a photoreceptor-like to a conventional neuron-like pathway by the basement membrane glycoprotein laminin. Unlike other cell systems where laminin influences differentiation, Y-79 cells can neither attach to nor chemotactically respond to laminin. However, laminin increases attachment to poly(D-lysine). The laminin effects therefore seem to occur via an adhesion- and chemotaxis-independent mechanism. Moreover, these tumor cells do not exhibit high-affinity laminin binding, having only a single binding site of intermediate affinity. Laminin-Sepharose affinity chromatography of Y-79 cell surface proteins labeled with 125I revealed a single major radiolabeled 100-kDa protein eluted by 20 mM EDTA, with an electrophoretic behavior different from that of integrins. No other proteins were eluted under more stringent conditions. This material, which we call LBM-100 (100-kDa laminin-binding molecule), may be a "differentiative" laminin-binding protein through which laminin influences gene expression and development independently of attachment.
 ...
PMID:Laminin-induced retinoblastoma cell differentiation: possible involvement of a 100-kDa cell-surface laminin-binding protein. 153 53

In an attempt to improve bifunctional chelate labelling of Mab, we investigated the use of a polyamino acid backbone for multiple DTPA substitutions. Poly-L-lysine (PL) (3.8 Kd, n = 25) was partially acetylated with MADTPA to yield 11 moles of DPTA per mole of PL. The average numbers of DTPA on PL were directly quantified with MADTPA-C-14. The remaining epsilon amino groups on PL-DTPA (I) were measured with TNBS reagent. A selective maleimide derivatization of (I) with S-SMPB yielded (II), which contains 2.3 moles of maleimide groups per mole of (I). The sulfhydryl activation of Mab-TP41.2F(ab')2 with 2-Iminothiolane hydrochloride produced (III), containing 1.3 moles of sulfhydryl groups per mole of Mab. Compounds (II) and (III) were combined to form a single thioether-spaced chain linkage of Mab-PL-DTPA (IV), which was subsequently chelated with 111In to yield (V), which was the compound of interest. Indium-111-PL-DTPA (VI) and 111In-DTPA-MabTP41.2F(ab')2 (VII) also were prepared for control studies. Direct cell binding assay revealed the mean immunoreactivity of (V) to be 79.4% and that of (VII) to be 39.5%. In a biodistribution study on melanoma tumor-bearing athymic mice at 4, 24, and 48 hr postinjection, the tumor/blood and tumor/liver ratios at 48 hr were 11.6 and 1.2 for (V), compared to 3.7 and 0.13, respectively, with (VII). Thus, the PL configuration for radiolabeled antibodies seems to result in decreased hepatic accumulation and retained tumor activity. The findings suggest that further studies of this new compound are warranted.
 ...
PMID:Reduced hepatic accumulation of radiolabeled monoclonal antibodies with indium-111-thioether-poly-L-lysine-DTPA-monoclonal antibody-TP41.2F(ab')2. 155 42

Renal mesenchymal tumors induced in F344 rats with methyl(methoxymethyl)nitrosamine (DMN-OMe) have previously been shown by our laboratory to contain transforming Ki-ras sequences, activated most commonly by a variety of codon 12 mutations. Further sequence analysis of the one DMN-OMe-induced tumor with transforming Ki-ras sequences detected by NIH 3T3 transfection assay but with no mutation in codon 12 detected by selective oligonucleotide hybridization has now revealed an activating point mutation in codon 63. The observed GAG----AAG transition in codon 63, which replaces glutamic acid with lysine, was the only detectable mutation in exon 1 and 2 hotspot regions of Ki-ras in this tumor. The same mutation was also detected in Ki-ras sequences derived from first- and second-cycle transformants in NIH 3T3 transfection assays. Although random mutagenesis studies of cloned Ha-ras sequences by Fasano et al. (Proc Natl Acad Sci USA 81:4008-4012, 1984) had already indicated that GAG----AAG mutations in codon 63 of ras are transforming, this is the first demonstration of the natural occurrence of this particular activating mutation in a tumor.
 ...
PMID:Activating point mutation in Ki-ras codon 63 in a chemically induced rat renal tumor. 155 12

We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.
 ...
PMID:Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects. 159 17

In order to develop a rat model that reflects human weakly or nonimmunogenic tumor-host relationships and allows investigation of T-cell retargeting with bispecific monoclonal antibodies in vivo, we prepared several mixed hybridomas. One fusion partner was the anti-rat-T-cell receptor (TCR)-framework hybridoma R73 and the others were hybridomas producing antibodies against CC531, a Wag rat colon carcinoma. Stimulation of Wag rat spleen cells with immobilized R73 mAb and rIL-2 yielded predominantly CD8 positive effector T-lymphocytes, which lysed control P815 target cells efficiently in R73-mediated reverse antibody-dependent cellular cytotoxicity (ADCC). The capacity of these effectors to cause significant hybrid antibody-mediated lysis of CC531 emerged several days later, was critically dependent on prolonged stimulation with immobilized R73, and was associated with increased N-alfa-benzyloxycarbonyl-L-lysine thiobenzyl esterase content.
 ...
PMID:T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. I. Significant bispecific lysis of syngeneic colon carcinoma CC531 is critically dependent on prolonged preactivation of effector T-lymphocytes by immobilized anti-T-cell receptor antibody. 159 9

The first and essential step in normal sexual differentiation takes place during the 5th-6th week of gestation. The testis determining factor (TDF) directs the undifferentiated gonad into a testis, which secretes hormones responsible for normal male development. A new candidate for TDF has recently been reported, and it has been called the sex determining region of the Y (SRY). The hypothesis has been supported by the finding of XX individuals with SRY, and two females with 46,XY karyotype and a mutation in SRY. However, XX males without SRY has been reported, and the role of SRY still has to be determined. We have tested three human females with 46,XY karyotype and gonadal dysgenesis and two 46,XX males for the presence of SRY using the polymerase chain reaction and subsequent DNA sequencing. Both 46,XX males contained SRY, whereas one of the 46,XY females had suffered a point mutation in SRY changing a codon for lysine to a stop codon. This information supports the hypothesis that SRY is significant in normal male sex differentiation. The two remaining 46,XY individuals had an intact HMG box, but it is possible that a mutation may be found in a regulatory gene or further downstream in the gene regulatory cascade. Two patients including the one with a mutation in SRY had gonadoblastomas supporting the hypothesis that another gene on the Y-chromosome is involved in the pathogenesis of this neoplasia.
 ...
PMID:Analysis of the sex-determining region of the Y chromosome (SRY) in sex reversed patients: point-mutation in SRY causing sex-reversion in a 46,XY female. 161 28

Total parenteral nutrition (TPN) may enhance the growth of some tumors: this enhanced growth is associated with an increase in the erythrocyte polyamine levels. The effect of arginine in TPN on tumor growth was compared with ornithine using rats with a transplantable Ward colon tumor. The relationship of circulating arginine, ornithine, glutamine, and polyamines with tumor growth was investigated. For rats fed chow ad libitum, increasing tumor weights were associated with a linear decrease in the plasma arginine levels which was consistently lower than that of age-matched non-tumor bearing (NTB) rats; ornithine and lysine levels were not affected. Subsequent experiments suggest that plasma glutamine levels were also lower in tumor bearing rats. Pair-fed NTB rats had reduced arginine but not glutamine levels in plasma. TPN regimens with arginine or with ornithine substituted for arginine at two levels (equimolar [Orn-Em] or isonitrogenous [Orn-IN]) were given to colon tumor bearing rats for 8 days. The final tumor weight of rats which received the arginine-containing regimen (19.8 +/- 5.7 g, n = 4) (P less than 0.05) was significantly greater than the tumor weight of rats fed chow ad libitum (12.1 +/- 3.3 g, n = 6). The final tumor weights of Orn-EM (11.2 +/- 2.6 g, n = 4) or Orn-IN (11.6 +/- 0.8 g, n = 6) were similar to the chow-fed controls. The plasma arginine levels were elevated, compared with the control, when arginine was present in the regimen. The plasma arginine levels of rats which received Orn-EM or Orn-IN were lower than the controls. The plasma ornithine levels were not affected by arginine in the regimen but were elevated with increasing levels of ornithine in TPN. Plasma glutamine levels were decreased when arginine was present in the regimen but were elevated when ornithine was substituted for arginine. Erythrocyte putrescine was increased when either arginine or ornithine was included in the TPN regimens. These results demonstrate that while arginine in a parenteral regimen stimulates tumor growth, substituting ornithine for arginine in TPN does not enhance the growth of a transplantable colon tumor.
 ...
PMID:Substituting ornithine for arginine in total parenteral nutrition eliminates enhanced tumor growth. 161 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>